1. Field of the Invention
The present invention relates to a new valuable process for the preparation of 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1-propanol and acid-addition salts thereof. This compound is called ifenprodil and is useful as a therapeutic agent for the treatment of cerebrovascular diseases.
2. Description of the Prior Art
1-(4-Hydroxyphenyl)-2-(4-benzylpiperidino)-1-propanol which is referred to hereinafter as ifenprodil is known and is represented by the structural formula: ##STR1##
All the processes known hitherto for preparing ifenprodil produce .alpha.-bromo-4'-benzyloxypropiophenone as an intermediate product (e.g. Japanese Patent Publn. No. 15348/72 and Japanese Laid-open Patent Appln. No. 4081/75). According to these prior art processes wherein 4'-hydroxypropiophenone is used as the main starting material, ifenprodil is prepared only by passing through the steps of benzylating the starting material to form 4'-benzyloxypropiophenone and then brominating the latter to obtain .alpha.-bromo-4'-benzyloxypriophenone. The benzyloxy group formed in the 4-position of the phenyl ring by the benzylation prior to the bromination is after all debenzylated in the posterior step so that the 4-position is again occupied by the hydroxyl group in ifenprodil which is the objective product of the reaction. The reason why such benzylation, which rather seems to be unnecessary, has to be carried out in the 4-position prior to the bromination is that when 4'-hydroxypropiophenone is directly subjected to bromination, the bromine-substitution tends to take place rather easily on the phenyl ring, thus making it difficult to attain the desired bromine-substitution in the .alpha.-position. However, the benzyloxy group in 4'-benzyloxypropiophenone formed as an intermediate is after all to be converted into the hydroxy group before obtaining ifenprodil, the end product. To say it in another way, the hydroxy group in the starting 4'-hydroxypropiophenone is once converted by the benzylation into the benzyloxy group for the purpose of protecting the phenyl ring from any ring-bromination and the protective benzyl group once introduced has to be split off before obtaining ifenprodil.
If elimination of such temporarily protecting steps for introducing and removing the benzyl group is possible in the preparation of ifenprodil from 4'-hydroxypropiophenone, it will apparently bring about outstanding advantages in the efficiency of a procedure for preparing ifenprodil. Heretofore, however, no study has been reported on the elimination of such protecting steps in the prior art processes for preparing ifenprodil.
Thus, there is still a great demand in this art for developing a new process which can obviate the disadvantages of the prior art processes and by which ifenprodil can be prepared in a high yield by a simple and economical means.